Skip to main content Accessibility help
×
Home

Genetic overlap between episodic memory deficits and schizophrenia: results from The Maudsley Twin Study

  • S. F. Owens (a1), M. M. Picchioni (a2), F. V. Rijsdijk (a3), D. Stahl (a4), E. Vassos (a1), A. K. Rodger (a1), D. A. Collier (a3), R. M. Murray (a1) and T. Toulopoulou (a1)...

Abstract

Background

Visual and verbal episodic memory deficits are putative endophenotypes for schizophrenia; however, the extent of any genetic overlap of these with schizophrenia is unclear. In this study, we set out to quantify the genetic and environmental contributions to variance in visual and verbal memory performance, and to quantify their genetic relationship with schizophrenia.

Method

We applied bivariate genetic modelling to 280 twins in a classic twin study design, including monozygotic (MZ) and dizygotic (DZ) pairs concordant and discordant for schizophrenia, and healthy control twins. We assessed episodic memory using subtests of the Wechsler Memory Scale – Revised (WMS-R).

Results

Genetic influences (i.e. heritability) contributed significantly to variance in immediate recall of both verbal memory and visual learning, and the delayed recall of verbal and visual memory. Liability to schizophrenia was associated with memory impairment, with evidence of significant phenotypic correlations between all episodic memory measures and schizophrenia. Genetic factors were the main source of the phenotypic correlations for immediate recall of visual learning material; both immediate and delayed recall of verbal memory; and delayed recall of visual memory that, for example, shared genetic variance with schizophrenia, which accounted for 88% of the phenotypic correlation (rph=0.41) between the two.

Conclusions

Verbal memory and visual learning and memory are moderately heritable, share a genetic overlap with schizophrenia and are valid endophenotypes for the condition. The inclusion of these endophenotypes in genetic association studies may improve the power to detect susceptibility genes for schizophrenia.

Copyright

Corresponding author

*Address for correspondence: Ms. S. F. Owens, Department of Psychosis Studies, Institute of Psychiatry, King's College London, King's Health Partners, De Crespigny Park, London SE5 8AF, UK. (Email: sheena.owens@kcl.ac.uk)

References

Hide All
Aleman, A, Hijman, R, De Haan, EHF, Kahn, RS (1999). Memory impairment in schizophrenia: a meta-analysis. American Journal of Psychiatry 156, 13581366.
Andreasen, NC (1984 a). Scale for the Assessment of Negative Symptoms. University of Iowa Press: Iowa City.
Andreasen, NC (1984 b). Scale for the Assessment of Positive Symptoms. University of Iowa Press: Iowa City.
Blyler, CR, Gold, JM (2000). Cognitive effects of typical antipsychotic treatment: another look. In Cognition in Schizophrenia: Impairments, Importance and Treatment Strategies (ed. Sharma, T. and Harvey, P. D.), pp. 241265. Oxford University Press: New York.
Cannon, M, Caspi, A, Moffitt, TE, Harrington, H, Taylor, A, Murray, RM, Poulton, R (2002). Evidence for early-childhood, pan-developmental impairment specific to schizophreniform disorder: results from a longitudinal birth cohort. Archives of General Psychiatry 59, 449456.
Cannon, TD (2005). The inheritance of intermediate phenotypes for schizophrenia. Current Opinion in Psychiatry 18, 135140.
Cannon, TD, Huttunen, MO, Lonnqvist, J, Tuulio-Henriksson, A, Pirkola, T, Glahn, D, Finkelstein, J, Hietanen, M, Kaprio, J, Koskenvuo, M (2000). The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia. American Journal of Human Genetics 67, 369382.
Cannon, TD, Keller, MC (2006). Endophenotypes in the genetic analyses of mental disorders. Annual Review of Clinical Psychology 2, 267290.
Cannon, TD, Hennah, W, van Erp, TG, Thompson, PM, Lonnqvist, J, Huttunen, M, Gasperoni, T, Tuulio-Henriksson, A, Pirkola, T, Toga, AW, Kaprio, J, Mazziotta, J, Peltonen, L (2005). Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Archives of General Psychiatry 62, 12051213.
Chen, L-S, Rice, TK, Thompson, PA, Barch, DM, Csernansky, JG (2009). Familial aggregation of clinical and neurocognitive features in sibling pairs with and without schizophrenia. Schizophrenia Research 111, 159166.
Cirillo, MA, Seidman, LJ (2003). Verbal declarative memory dysfunction in schizophrenia: from clinical assessment to genetics and brain mechanisms. Neuropsychology Review 13, 4377.
Cohen, DJ, Dibble, E, Grawe, JM, Pollin, W (1975). Reliably separating identical from fraternal twins. Archives of General Psychiatry 32, 13711375.
Dempster, EL, Toulopoulou, T, McDonald, C, Bramon, E, Walshe, M, Wickham, H, Sham, PC, Murray, RM, Collier, DA (2006). Episodic memory performance predicted by the 2bp deletion in exon 6 of the ‘alpha 7-like’ nicotinic receptor subunit gene. American Journal of Psychiatry 163, 18321834.
Dickinson, D, Ramsey, ME, Gold, JM (2007). Overlooking the obvious: a meta-analytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia. Archives of General Psychiatry 64, 532542.
Elvevag, B, Goldberg, TE (2000). Cognitive impairment in schizophrenia is the core of the disorder. Critical Reviews in Neurobiology 14, 121.
Fioravanti, M, Carlone, O, Vitale, B, Cinti, ME, Clare, L (2005). A meta-analysis of cognitive deficits in adults with a diagnosis of schizophrenia. Neuropsychology Review 15, 7395.
First, MB, Spitzer, RL, Gibbon, M, Williams, JBM (1997). Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). New York State Psychiatric Institute: New York.
Glahn, DC, Almasy, L, Blangero, J, Burk, GM, Estrada, J, Peralta, JM, Meyenberg, N, Castro, MP, Barrett, J, Nicolini, H, Raventós, H, Escamilla, MA (2007). Adjudicating neurocognitive endophenotypes for schizophrenia. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 144B, 242249.
Goldberg, TE, Egan, MF, Gscheidle, T, Coppola, R, Weickert, T, Kolachana, BS, Goldman, D, Weinberger, DR (2003). Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Archives of General Psychiatry 60, 889896.
Goldberg, TE, Ragland, JD, Torrey, EF, Gold, JM, Bigelow, LB, Weinberger, DR (1990). Neuropsychological assessment of monozygotic twins discordant for schizophrenia. Archives of General Psychiatry 47, 10661072.
Goldberg, TE, Torrey, EF, Gold, JM, Ragland, JD, Bigelow, LB, Weinberger, DR (1993). Learning and memory in monozygotic twins discordant for schizophrenia. Psychological Medicine 23, 7185.
Gottesman, II, Gould, TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636645.
Greenwood, TA, Braff, DL, Light, GA, Cadenhead, KS, Calkins, ME, Dobie, DJ, Freedman, R, Green, MF, Gur, RE, Gur, RC, Mintz, J, Nuechterlein, KH, Olincy, A, Radant, AD, Seidman, LJ, Siever, LJ, Silverman, JM, Stone, WS, Swerdlow, NR, Tsuang, DW, Tsuang, MT, Turetsky, BI, Schork, NJ (2007). Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia. Archives of General Psychiatry 64, 12421250.
Gur, RE, Nimgaonkar, VL, Almasy, L, Calkins, ME, Ragland, JD, Pogue-Geile, MF, Kanes, S, Blangero, J, Gur, RC (2007). Neurocognitive endophenotypes in a multiplex multigenerational family study of schizophrenia. American Journal of Psychiatry 164, 813819.
Hall, M-H, Rijsdijk, F, Picchioni, M, Schulze, K, Ettinger, U, Toulopoulou, T, Bramon, E, Murray, RM, Sham, P (2007). Substantial shared genetic influences on schizophrenia and event-related potentials. American Journal of Psychiatry 164, 804812.
Hardin, JW, Hilbe, JM (2003). Generalized Estimating Equations. Chapman & Hall/CRC: Boca Raton, FL.
Heaton, RK, Gladsjo, JA, Palmer, BW, Kuck, J, Marcotte, TD, Jeste, DV (2001). Stability and course of neuropsychological deficits in schizophrenia. Archives of General Psychiatry 58, 2432.
Heinrichs, RW, Zakzanis, KK (1998). Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 12, 426445.
Husted, JA, Lim, S, Chow, EWC, Greenwood, C, Bassett, AS (2009). Heritability of neurocognitive traits in familial schizophrenia. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 150B, 845853.
Jones, P, Rodgers, B, Murray, R, Marmot, M (1994). Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 344, 13981402.
Keller, MC, Coventry, WL (2005). Quantifying and addressing parameter indeterminacy in the classical twin design. Twin Research and Human Genetics 8, 201213.
Lichtenstein, P, Yip, BH, Björk, C, Pawitan, Y, Cannon, TD, Sullivan, PF, Hultman, CM (2009). Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373, 234239.
Martin, N, Boomsma, D, Machin, G (1997). A twin-pronged attack on complex traits. Nature Genetics 17, 387392.
Neale, MC (1999). Mx: Statistical Modelling. Department of Psychiatry, Medical College of Virginia: Richmond, VA.
O'Donovan, MC, Craddock, N, Norton, N, Williams, H, Peirce, T, Moskvina, V, Nikolov, I, Hamshere, M, Carroll, L, Georgieva, L, Dwyer, S, Holmans, P, Marchini, JL, Spencer, CCA, Howie, B, Leung, H-T, Hartmann, AM, Moller, H-J, Morris, DW, Shi, Y, Feng, G, Hoffmann, P, Propping, P, Vasilescu, C, Maier, W, Rietschel, M, Zammit, S, Schumacher, J, Quinn, EM, Schulze, TG, Williams, NM, Giegling, I, Iwata, N, Ikeda, M, Darvasi, A, Shifman, S, He, L, Duan, J, Sanders, AR, Levinson, DF, Gejman, PV, Cichon, S, Nothen, MM, Gill, M, Corvin, A, Rujescu, D, Kirov, G, Owen, MJ (2008). Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nature Genetics 40, 10531055.
Prasad, KM, Chowdari, KV, Nimgaonkar, VL, Talkowski, ME, Lewis, DA, Keshavan, MS (2005). Genetic polymorphisms of the RGS4 and dorsolateral prefrontal cortex morphometry among first episode schizophrenia patients. Molecular Psychiatry 10, 213219.
Rabe-Hesketh, S, Skrondal, A (2005). Multilevel and Longitudinal Modeling using Stata. Stata Press: College Station, TX.
Reichenberg, A, Harvey, PD (2007). Neuropsychological impairments in schizophrenia: integration of performance-based and brain imaging findings. Psychological Bulletin 133, 833858.
Rijsdijk, FV, Sham, PC (2002). Analytic approaches to twin data using structural equation models. Briefings in Bioinformatics 3, 119133.
Rijsdijk, FV, van Haren, NEM, Picchioni, MM, McDonald, C, Toulopoulou, T, Hulshoff Pol, HE, Kahn, RS, Murray, R, Sham, PC (2005). Brain MRI abnormalities in schizophrenia: same genes or same environment? Psychological Medicine 35, 13991409.
Simes, RJ (1986). An improved Bonferroni procedure for multiple tests of significance. Biometrika 73, 751754.
Sitskoorn, MM, Aleman, A, Ebisch, SJH, Appels, MCM, Kahn, RS (2004). Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis. Schizophrenia Research 71, 285295.
Spitzer, RL, Endicott, J (1978). Schedule for Affective Disorders and Schizophrenia – Lifetime Version. New York State Psychiatric Institute: New York.
Stefansson, H, Rujescu, D, Cichon, S, Pietilainen, OPH, Ingason, A, Steinberg, S, Fossdal, R, Sigurdsson, E, Sigmundsson, T, Buizer-Voskamp, JE, Hansen, T, Jakobsen, KD, Muglia, P, Francks, C, Matthews, PM, Gylfason, A, Halldorsson, BV, Gudbjartsson, D, Thorgeirsson, TE, Sigurdsson, A, Jonasdottir, A, Jonasdottir, A, Bjornsson, A, Mattiasdottir, S, Blondal, T, Haraldsson, M, Magnusdottir, BB, Giegling, I, Moller, H-J, Hartmann, A, Shianna, KV, Ge, D, Need, AC, Crombie, C, Fraser, G, Walker, N, Lonnqvist, J, Suvisaari, J, Tuulio-Henriksson, A, Paunio, T, Toulopoulou, T, Bramon, E, Di Forti, M, Murray, R, Ruggeri, M, Vassos, E, Tosato, S, Walshe, M, Li, T, Vasilescu, C, Muhleisen, TW, Wang, AG, Ullum, H, Djurovic, S, Melle, I, Olesen, J, Kiemeney, LA, Franke, B, Sabatti, C, Freimer, NB, Gulcher, JR, Thorsteinsdottir, U, Kong, A, Andreassen, OA, Ophoff, RA, Georgi, A, Rietschel, M, Werge, T, Petursson, H, Goldstein, DB, Nothen, MM, Peltonen, L, Collier, DA, St Clair, D, Stefansson, K (2008). Large recurrent microdeletions associated with schizophrenia. Nature 455, 232236.
Sullivan, PF, Kendler, KS, Neale, MC (2003). Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Archives of General Psychiatry 60, 11871192.
Tan, HY, Callicott, JH, Weinberger, DR (2008). Intermediate phenotypes in schizophrenia genetics redux: is it a no brainer? Molecular Psychiatry 13, 233238.
Toulopoulou, T, Picchioni, M, Rijsdijk, F, Hua-Hall, M, Ettinger, U, Sham, P, Murray, R (2007). Substantial genetic overlap between neurocognition and schizophrenia: genetic modeling in twin samples. Archives of General Psychiatry 64, 13481355.
Toulopoulou, T, Quraishi, S, McDonald, C, Murray, RM (2006). The Maudsley Family Study: premorbid and current general intellectual function levels in familial bipolar I disorder and schizophrenia. Journal of Clinical and Experimental Neuropsychology 28, 243259.
Tuulio-Henriksson, A, Haukka, J, Partonen, T, Varilo, T, Paunio, T, Ekelund, J, Cannon, TD, Meyer, JM, Jouko, L (2002). Heritability and number of quantitative trait loci of neurocognitive functions in families with schizophrenia. American Journal of Medical Genetics 114, 483490.
Wechsler, D (1987). Manual for the Wechsler Memory Scale – Revised. The Psychological Corporation: San Antonio, TX.
Wechsler, D (1997). Wechsler Adult Intelligence Scale, Third Edition: Administration and Scoring Manual. The Psychological Corporation: London, UK.
Williams, RL (2000). A note on robust variance estimation for cluster-correlated data. Biometrics 56, 645646.

Keywords

Type Description Title
WORD
Supplementary materials

Owens Supplementary Material
Table.doc

 Word (68 KB)
68 KB

Genetic overlap between episodic memory deficits and schizophrenia: results from The Maudsley Twin Study

  • S. F. Owens (a1), M. M. Picchioni (a2), F. V. Rijsdijk (a3), D. Stahl (a4), E. Vassos (a1), A. K. Rodger (a1), D. A. Collier (a3), R. M. Murray (a1) and T. Toulopoulou (a1)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed